Measles outbreaks continue to occur in unimmunized children and in older vaccines due to primary vaccine failure or waning immunity. Achieving protective immunity across all age groups requires several strategies including a better understanding of the optimal age for immunizing young infants, the optimal age for reimmunization, and knowledge about the factors that might enhance or diminish the response to currently available vaccines. Towards this end, this laboratory collaborates with several clinical investigators to evaluate the immune response to measles vaccine. In collaboration with Dr. Henry Pabst, we have completed studies that define the kinetics of the humoral and cell mediated immune response to the first dose of measles containing vaccine in 12 month old children. 80 children were immunized with vaccine containing the Moraten strain of measles virus and followed serially for 38 days. Neutralizing antibody and CMI response to measles HA plateaued by 28 days after immunization. Lymphoproliferative responses to tetanus and candida were depressed at 14 days after immunization but returned to baseline by day 38. The response to recall antigens were depressed 10-20%; in contrast, responses were depressed 80-90% following wild type infection. The predominant cytokine expressed by PBMCs after immunization was IFN-gamma with no change in IL4 or IL10 secretion suggesting that primary measles immunization primes for a predominantly TH1 type response. The impact of vitamin A supplementation on primary measles immunization (Schwarz strain) was studied in a placebo controlled double-blind trial in 9 month old infants in Indonesia in collaboration with Dr. Richard Semba. There was no significant difference between the vitamin treated and control groups in seroconversion rates or percent achieving protective neutralizing antibody titers. However, GMTs for infants in the placebo group who had maternal antibody at the time of immunization were higher than the GMTs for antibody positive infants in the vitamin a treated group suggesting synergy between passively acquired antibody and vitamin A in limiting vaccine virus replication. Studies to evaluate the optimal age for the second dose of measles vaccine are currently underway. Preliminary analysis of sera from over 237 children indicates that the second dose of measles vaccine is successful in seroconverting all children with primary vaccine failure and increases the percent with titers >120 from 94 to 99%. This level of immunity is necessary to achieve measles eradication in the US.